University Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Vienna, Austria.
Clinic for Swine, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-University Munich, Oberschleissheim, Germany.
Front Immunol. 2022 Nov 8;13:1055048. doi: 10.3389/fimmu.2022.1055048. eCollection 2022.
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating viruses for the global swine industry. Infection during late gestation causes reproductive failure but the local immune response remains poorly understood. In this study, an experimental PRRSV-infection model with two different PRRSV-1 field isolates was used to investigate the immune cell phenotypes at the maternal-fetal interface during late gestation. In addition, phenotypic changes induced by a modified live virus (MLV, ReproCyc PRRS EU) vaccine were studied. Vaccinated (n = 12) and non-vaccinated pregnant gilts (n = 12) were challenged with either one of the PRRSV-1 field isolates (low vs. high virulent, LV or HV) or sham-inoculated at day 84 of gestation. Twenty-one days post infection all gilts were euthanized and the fetal preservation status for all fetuses per litter was assessed. Leukocytes from the maternal-fetal interface were isolated and PRRSV-induced changes were investigated using phenotyping by flow cytometry. PRRSV load in tissue from the maternal endometrium (ME) and fetal placenta (FP) was determined by RT-qPCR. In the ME, a vast increase in CD8β T cells with CD8αCD27 early effector phenotype was found for fetuses from the non-vaccinated LV and HV-challenged gilts, compared to non-treated and vaccinated-only controls. HV-challenged fetuses also showed significant increases of lymphocytes with effector phenotypes in the FP, including NKp46 NK cells, CD8α γδ T cells, as well as CD8αCD27 CD4 and CD8 T cells. In vaccinated animals, this common activation of effector phenotypes was more confined and the fetal preservation status significantly improved. Furthermore, a negative correlation between the viral load and CD163CD169 mononuclear phagocytic cells was observed in the FP of HV-infected animals. These results suggest that the strong expansion of effector lymphocytes in gilts that were only infected causes immune-pathogenesis rather than protection. In contrast, the attenuated MLV seems to dampen this effect, yet presumably induces memory cells that limit reproductive failure. This work provides valuable insights into changes of local immune cell phenotypes following PRRSV vaccination and infection.
猪繁殖与呼吸综合征病毒（PRRSV）是全球养猪业最具破坏性的病毒之一。妊娠后期感染会导致繁殖失败，但局部免疫反应仍知之甚少。在这项研究中，使用两种不同的 PRRSV-1 田间分离株建立了一个实验性 PRRSV 感染模型，以研究妊娠后期母胎界面的免疫细胞表型。此外，还研究了改良活病毒（MLV，ReproCyc PRRS EU）疫苗引起的表型变化。接种（n=12）和未接种（n=12）妊娠母猪在妊娠第 84 天分别用 PRRSV-1 田间分离株之一（低毒力与高毒力，LV 或 HV）或假感染进行攻毒。感染后第 21 天，所有母猪被安乐死，并评估每个窝的所有胎儿的保存状态。从母胎界面分离白细胞，并通过流式细胞术表型分析研究 PRRSV 诱导的变化。通过 RT-qPCR 测定母体子宫内膜（ME）和胎儿胎盘（FP）组织中的 PRRSV 载量。在 ME 中，与未处理和仅接种疫苗的对照组相比，来自未接种 LV 和 HV 攻毒母猪的胎儿中，CD8β T 细胞与 CD8αCD27 早期效应表型的大量增加。HV 攻毒的胎儿在 FP 中也表现出具有效应表型的淋巴细胞显著增加，包括 NKp46 NK 细胞、CD8αγδ T 细胞以及 CD8αCD27 CD4 和 CD8 T 细胞。在接种动物中，这种效应表型的共同激活受到限制，胎儿保存状态显著改善。此外，在 HV 感染动物的 FP 中观察到病毒载量与 CD163CD169 单核吞噬细胞之间存在负相关。这些结果表明，仅感染的母猪中效应淋巴细胞的强烈扩增会引起免疫发病机制而不是保护。相反，减毒 MLV 似乎抑制了这种效应，但可能诱导了限制繁殖失败的记忆细胞。这项工作为 PRRSV 接种和感染后局部免疫细胞表型的变化提供了有价值的见解。
